Hemostasis and thrombosis

Question 1

Phases of blood clotting

Answer 1

1. Local vasoconstriction
2. Platelet aggregation
    antiplatelet agents
3. Coagulation cascade
    anticoagulants
4. Thrombolysis
    thrombolytic agents

Question 2

Antiplatelet agents

• receptors
• Types of antiplatelet agents

Answer 2

GpIIA-IIIB receptors on the surface! –> crosslinkings

1. Cyclooxigenase inhibitors (COX inhibitors)
2. ADP receptor inhibitors (clopidogrel)

Question 3

Antiplatelet agents

• COX inhibitors
  - Type
  - Indications
  - Side effects

Answer 3

Acetylsalicilyic acid (Aspirin®)
Low dose, irreversible COX-1 inhibitor
Platelet Ø DNS —> no COX-synthesis
Long (7-10 days) duration!

Indications:
- feline HCM 
- Dogs DIC and heartworm
- Human
Side effects (H2 antagonists!)

Question 4

ADP receptor inhibitors

- uses

Answer 4

used in the treatment of acute coronary syndrome (ACS) or in preventive treatment for patients who are in risk of thromboembolism, myocardial infarction or a stroke

Question 5

ADP receptor inhibitors

- Drug example, uses

Answer 5

lopidogrel (Plavix® tablet)
more veterinary experience
prodrug (liver)
less frequent side effects (anorexia, GI —> food)

Question 6

Vit. K antagonists affect which factors?

- example: kinetics, indications, side effects

Answer 6

Function: II, VII, IX, X clotting factor carboxylation

Warfarin
VII: half life 6 hours
Onset of action 18-24 hours
Kinetics
	orally, IM., IV.
	extensive protein binding! ---> interactions!
Indications (rare!)
	cat HCM 
	dog thromboembolism 
Side effects 
	bleedings (PI time) ---> plasma transfusion
	pregnancy

Question 7

Heparin:

• produced by?
• Types

Answer 7

Produced by mast cells
Acidic —> anionic

1. Heterogenic substances between 1-30 KDa (non fractionated heparin)
   average 20 KDa
2. Low molecular weight heparin (LMWH)
   average 3-4 KDa

Question 8

Heparin mechanism of action:

Answer 8

• Antithrombin
  thrombin + VII, IX, X and XII clotting factor inactivation
• Antithrombin (+) and heparin (-) complex —> conformational change —> 1000x acceleration!

Inhibition depends on the molecular weight!
Non fractionated = thrombin + Xa + others
LMWH = primarily Xa + thrombin + others
LMWH: better selectivity
Larger therapeutic index (bleeding occurrence decreased)

Question 9

Heparin substances

Answer 9

Substances
Non fractionated: Na-heparin, Ca-heparin
LMWH: dalteparin, fraxiparin, enoxaparin

suspending action: protamine

Question 10

Heparin indications:

• other uses
• admin

Answer 10

Indications
 Feline HCM thromboembolism
 DIC
 Heartworm (Dirofilaria immitis)
	Ca, Fe:  SC. or IV. (im. Ø)
	Eq:  SC. or IV.
- No oral absorption, SC. poor absorption
Other usage
Vacutainers (Li-heparin)
Flushing catheters

Question 11

Streptokinase

Answer 11

Streptococcus spp.
Plasminogen is activated to plasmin
Antigen –> immune response (4-7 days) –>anaphylaxis!
Non-selective for thrombi = bleedings

Ho: pulmonary embolism, heart infarction
Ca. 90000 NE/kg iv. in infusion (30 mins)
Fe?: 45000-90000 NE/kg (1 hours)
REPERFUSION!

Question 12

Tissue plasminogen activator (t-PA) analogues

Answer 12

Ø immunological reaction!
- Alteplas (recombinant t-PA) : spontaneous bleedings
- Tenecteplas
- Reteplas
Ho: pulmonary embolism, heart infarction

Question 13

Inhibitors of anticoagulants and other agents for reducing bleeding:

Answer 13

- Protamine
Protein, chemical antagonist of heparin 
Standard > LMWH
Fondaparinux Ø
50% of heparin dosage
Intravenous, slow infusion

Etamsylat
Capillary wall integrity decreased
PGI (prostaglandin) effect inhibition!
Effects: decreased bleeding time, but PI, APTI not changing
Side effect rare, large therapeutic index
PO., IM., IV.
5-10 mg/kg